Abstract

Alpha-mannosidosis is an inherited lysosomal storage disorder characterized by immune
deficiency, facial and skeletal abnormalities, hearing impairment, and intellectual
disability. It occurs in approximately 1 of 500,000 live births. The children are
often born apparently normal, and their condition worsens progressively. Some children
are born with ankle equinus or develop hydrocephalus in the first year of life. Main
features are immune deficiency (manifested by recurrent infections, especially in
the first decade of life), skeletal abnormalities (mild-to-moderate dysostosis multiplex,
scoliosis and deformation of the sternum), hearing impairment (moderate-to-severe
sensorineural hearing loss), gradual impairment of mental functions and speech, and
often, periods of psychosis. Associated motor function disturbances include muscular
weakness, joint abnormalities and ataxia. The facial trait include large head with
prominent forehead, rounded eyebrows, flattened nasal bridge, macroglossia, widely
spaced teeth, and prognathism. Slight strabismus is common. The clinical variability
is significant, representing a continuum in severity. The disorder is caused by lysosomal
alpha-mannosidase deficiency. Alpha-mannosidosis is inherited in an autosomal recessive
fashion and is caused by mutations in the MAN2B1 gene located on chromosome 19 (19 p13.2-q12). Diagnosis is made by measuring acid
alpha-mannosidase activity in leukocytes or other nucleated cells and can be confirmed
by genetic testing. Elevated urinary secretion of mannose-rich oligosaccharides is
suggestive, but not diagnostic. Differential diagnoses are mainly the other lysosomal
storage diseases like the mucopolysaccharidoses. Genetic counseling should be given
to explain the nature of the disease and to detect carriers. Antenatal diagnosis is
possible, based on both biochemical and genetic methods. The management should be
pro-active, preventing complications and treating manifestations. Infections must
be treated frequently. Otolaryngological treatment of fluid in the middle ear is often
required and use of hearing aids is invariably required. Early educational intervention
for development of social skills is needed and physiotherapy is important to improve
bodily function. Orthopedic surgery may be necessary. The long-term prognosis is poor.
There is an insidiously slow progression of neuromuscular and skeletal deterioration
over several decades, making most patients wheel-chair dependent. No patients manage
to be completely socially independent. Many patients are over 50 years of age.